Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells

Wack, Andreas; Soldaini, Elisabetta; Tseng, Chien Te K.; Nuti, Sandra; Klimpel, Gary R.; Abrignani, Sergio

doi:10.1002/1521-4141(200101)31:1<166::aid-immu166>3.0.co;2-l

Cited by 142 publications

(126 citation statements)

References 35 publications

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“…The current study confirms previous findings (16,17,24) of the T-cell costimulatory effect mediated by CD81. We found that dual costimulation through CD81 and CD28 induced a greater number of activated cells than that induced through each of these costimulatory molecules alone.…”

Section: Kinetics Of Early Signaling Events In T-cell Activation Depesupporting

confidence: 93%

“…2C). Individually, an anti-CD81 mAb (5A6 or 1D6) increased the number of activated cells with a magnitude similar to costimulation by the anti-CD28 mAb, as has been reported (16)(17)(18)24). However, IFNγ was better produced following CD28 costimulation possibly due to stronger activation of NFκB (Fig.…”

Section: Kinetics Of Early Signaling Events In T-cell Activation Depesupporting

confidence: 72%

“…However, additional members of the CD28 family, such as ICOS and several members of the TNF family, such as CD27 and CD137 (4-1BB) are well known T-cell costimulatory molecules (13,14). Less investigated is the costimulatory effect of the tetraspanin family of molecules, including CD9, CD53, CD63, CD81 and CD82 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Interestingly, costimulation either by CD9 or by CD81 occurs in CD28-deficient T cells, suggesting either a different or a redundant activation pathway (18,19).…”

Section: A Ctivation Of Naïve T Cells Requires Two Independent Signalsmentioning

confidence: 99%

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Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

Sagi¹,

Landrigan

Levy³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells: Primary human naïve T cells are better costimulated by CD81, whereas the memory T-cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naïve T cells by CD81 was due to prolonged signal transduction compared with that by CD28. We found that IL-6 played a role in the activation of the naïve T-cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on Tcell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T-cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naïve T cells with their broad repertoire.

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Section: Kinetics Of Early Signaling Events In T-cell Activation Depesupporting

confidence: 93%

Section: Kinetics Of Early Signaling Events In T-cell Activation Depesupporting

confidence: 72%

Section: A Ctivation Of Naïve T Cells Requires Two Independent Signalsmentioning

confidence: 99%

See 1 more Smart Citation

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

Sagi¹,

Landrigan

Levy³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Interplay between HCV and CD81 expressed on PBMC has been related to HCV persistence as well as modulation of extrahepatic manifestations of chronic HCV infection [16][17][18][19][20]27].…”

Section: Discussionmentioning

confidence: 99%

“…CD81 is of particular interest because CD81 is not only expressed on hepatocytes but also on peripheral blood mononuclear cells (PBMC). Interaction of HCV with CD81 expressed on PBMC was suggested to be involved in an attenuated innate and adaptive immune response against HCV as well as in development of extrahepatic HCV manifestations [16][17][18][19][20]. However, these results were challenged by a recent study showing that HCV envelope 2 proteins have no modulatory effect on natural killer cell functions when expressed as part of cell culture infectious viral particles [21].…”

Section: Introductionmentioning

confidence: 99%

876 Soluble Serum Cd81 Is Elevated in Patients With Chronic Hepatitis C and Correlates With Alanine Aminotransferase Serum Activity

Welker¹,

Reichert²,

Susser³

et al. 2012

Journal of Hepatology

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Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity.Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry.Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p.0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027).Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis.

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Immune Mechanisms of Viral Clearance and Disease Pathogenesis During Viral Hepatitis

Ferrari

Mondelli

2009

The Liver

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Binding of the hepatitis C virus envelope protein E2 to CD81 provides a co-stimulatory signal for human T cells

Cited by 142 publications

References 35 publications

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81

876 Soluble Serum Cd81 Is Elevated in Patients With Chronic Hepatitis C and Correlates With Alanine Aminotransferase Serum Activity

Immune Mechanisms of Viral Clearance and Disease Pathogenesis During Viral Hepatitis

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